Search PubMed⌕ Search

Biomedical subjects

H Tsuda

Publications and source records attributed to H Tsuda.

At least 451 records · Page 25Linked to original sources
PubMed1990

NMDA-sensitive L-[3H]glutamate binding in cerebral cortex of El mice.

NMDA-sensitive L-[3H]glutamate binding was examined in the brains of El mice, a genetic animal model of epilepsy, and in ddY mice. In whole brain, Scatchard analysis showed that both stimulated and unstimulated El mice had significantly lower Bmax values for binding than did ddY mice. In regional studies, the binding of NMDA-sensitive L-[3H]glutamate was significantly less in the cerebral cortex of both stimulated and unstimulated El mice than in that of ddY mice. These data suggest that NMDA receptors may be involved in the genetic susceptibility of El mice to seizures.

Animals↗
PubMed1990

Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma.

Loss of heterozygosity on chromosome 16 is a common genetic alteration in human hepatocellular carcinoma (HCC). To clarify the pathogenetic significance of allele loss on chromosome 16, we performed restriction fragment length polymorphism analysis of 70 surgically resected tumors by using 15 polymorphic DNA markers for chromosome 16. Loss of heterozygosity on chromosome 16 was detected in 36 (52%) of 69 informative cases, and the common region of allele loss in these 36 tumors was located between the HP locus (16q22.1) and the CTRB locus (16q22.3-q23.2). These losses occurred more frequently in HCCs of poor differentiation, of larger size, and with metastasis, whereas they were not detected in HCC at the earliest stage. In addition, these losses were not associated with presence or absence of hepatitis B virus DNA integration or hepatitis C virus infection. These results show that loss of heterozygosity on chromosome 16 is a late event occurring after hepatocarcinogenesis and strongly suggest that this phenomenon is involved in enhancement of tumor aggressiveness during progression of HCC.

Alleles↗
PubMed1990

Lack of hepatotoxicity or promotion of enzyme-altered liver foci development in rats treated with harman or norharman.

The modifying effects of harman or norharman on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given harman or norharman at dietary levels of 1000 and 200 parts per million (ppm), or sodium phenobarbital (PB) at 500 ppm as a positive control, for 6 wk. At wk 3 following DEN administration, all animals were subjected to partial hepatectomy. Marked retardation of body weight gain was observed in rats treated with harman or norharman at 1000 ppm, but not at 200 ppm. Increased relative kidney but not liver weights were associated with harman or norharman treatment, especially in the higher dose groups. Although no toxicity-related hepatocyte lesions were found, severe renal toxic tubular lesions and regeneration were evident. Neither harman nor norharman significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive foci observed after DEN initiation, in clear contrast to PB. The results thus demonstrated that harman and norharman are nontoxic for the liver and lack modifying potential for liver carcinogenesis in our medium-term bioassay system.

Alkaloids↗
PubMed1990

Comparison of initiation potential of 2-amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in an in vivo carcinogen bioassay system.

A new approach to low-dose assessment of carcinogenic potential was applied to food contaminant pyrolysis products. Single intragastric doses of the carcinogenic pyrolysates, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline MeIQx), were given 12 h after two-thirds partial hepatectomy (PH) to F344 male rats. Two weeks thereafter the animals were placed on a basal diet containing 0.05% phenobarbital (PB) for 6 weeks combined with an i.p. administration of D-galactosamine (300 mg/kg) to facilitate growth of initiated cells. Both IQ and MeIQx clearly caused initiation of hepatocarcinogenesis as revealed by induction of preneoplastic placental-form glutathione-S-transferase-positive (GST-P+) hepatocyte foci composed of more than three cells (approximately 30 microns in diameter). A similar protocol without performance of PH before pyrolysate administration gave a positive result only for the IQ-treated group indicating that cell proliferation is essential during the low-dose, one-shot initiation step. IQ was found to be two to three times more potent in inducing GST-P+ foci using both protocols. The current approach could find application in practical carcinogenicity screening of chemicals, for which only small amounts are available.

Animals↗
PubMed1990

Malignant transformation of mouse BALB/c3T3 cells induced by NaNO2.

The addition of sodium nitrite (NaNO2; 5-20 mM) for 72 h to mouse BALB/c3T3 cells resulted in the induction of transformed foci (type III foci) in a dose-dependent manner. The cells isolated from the NaNO2-induced transformed foci produced progressively growing tumors when inoculated into nude mice subcutaneously at an inoculum size of 1 X 10(6) cells per site. In contrast, the original untreated cells did not take even at an inoculum size of 1 X 10(7) cells per site. The possibility that NaNO2 might react with cellular or medium components to make carcinogenic N-nitrosamines and that these might induce cell transformation was examined and almost excluded. Thus, nitrite itself seems to have a cell transforming activity. Recent evidence suggests that NO2- is produced by the activated macrophages of mammals. We also detected NO2- production in culture media in the mouse macrophage-like cell line J774-A1 after lipopolysaccharide (LPS) treatment, and also in the human promyeloleukemia cell line HL60 after differentiation into macrophage-like cells by 12-O-tetradecanoyl phorbol-13-acetate and further activation by LPS.

Animals↗
PubMed1990

Frequent loss of heterozygosity on chromosomes 16 and 4 in human hepatocellular carcinoma.

By restriction fragment length polymorphism analysis, we examined loss of heterozygosity at 34 loci on 23 chromosomes in 35 surgically resected human hepatocellular carcinomas. Allele losses at the HP locus on chromosome 16q22 and at the MT2P1 locus on chromosome 4p11-q21 were detected in 57% (8/14) and 50% (8/16) of cases, respectively. Loss of heterozygosity on chromosomes 16q and 4 occurred simultaneously in 4 of 7 informative cases for both loci, and seemed to be important in the development of human hepatocellular carcinoma irrespective of the presence of hepatitis B virus infection. In contrast, the incidence of allele loss was low at the other loci, e.g., chromosome 1p, 3p, 11p, 13q or 17p, where one allele is frequently lost in other cancers.

Carcinoma, Hepatocellular↗
PubMed1990

Immunohistochemical study on overexpression of c-erbB-2 protein in human breast cancer: its correlation with gene amplification and long-term survival of patients.

Using a polyclonal antibody monospecific to the c-erbB-2 oncogene product, an immunohistochemical study on the expression of c-erbB-2 protein was performed in formalin-fixed, paraffin-embedded tissue sections from 176 primary breast carcinomas in which amplification of the c-erbB-2 gene had been detected in 28 cases. Expression of the c-erbB-2 protein was detected in 44 cases (25%), being strongly positive in 27 (15%) and weakly positive in 17 (10%). All cases with amplification of c-erbB-2 showed positive staining of its protein. There were only four cases in which c-erbB-2 was strongly expressed without amplification of the gene. In the group showing strongly positive staining, both overall and disease-free survival were significantly poorer than in the remainder of the cases. Using Cox's regression model analysis, overexpression of c-erbB-2 protein was demonstrated to be an effective prognostic factor independent of nodal status or tumor size.

Amino Acid Sequence↗
PubMed1990

Biochemical study on the critical period for treatment of the mottled brindled mouse.

Hemizygous mottled brindled mice (Mobr/y mice) were treated by subcutaneous injection of copper and were decapitated on postnatal day 14. Cytochrome c oxidase (COX) activity of the brain mitochondria in the mice given 10 micrograms of copper/g on day 4 or 7 showed significant increases compared with that of untreated Mobr/y animals, and these mice had no neurological symptoms. Mice given 10 micrograms of copper/g on day 12 showed neither increases in COX activity nor clinical improvement. The brain levels of copper, noradrenaline, and dopamine in the mice treated on day 12 were the same as those in animals treated on day 4 or 7. The in vitro activities of dopamine-beta-hydroxylase of the brain were also the same among the treated mice, irrespective of the date of treatment. The results indicate that delays in copper treatment produce irreversible changes in COX activity of the brain and lead to clinical unresponsiveness to treatment.

Animals↗
PubMed1990

Comparative sequential changes in serum and biliary levels of bile acid components after a single dose of D-galactosamine or partial hepatectomy in the rat.

In order to characterize changes in bile acid profile during liver cell damage and regeneration, levels of bile acids in serum and bile were determined by high performance liquid chromatography (HPLC) in F344 rats treated with a single dose of D-galactosamine (galactosamine, 300 mg/kg, i.p.) or subjected to two-thirds partial hepatectomy (PH). In the serum, galactosamine caused elevation of conjugated bile acids such as taurocholic acid (TCA) and tauro-beta-muricholic acid (T beta MCA) at the 24 and 48-h time points, whereas unconjugated bile acids including cholic acid (CA) at 24 h and hyodeoxycholic acid (HDCA) at 48 h were increased after PH. In the bile, elevation of TCA showed most remarkable elevation at the 24-h time point in the galactosamine-treated group. All components of biliary bile acids showed rapid decreases from 24 to 48 h. The results demonstrated that while liver tissue damaged by galactosamine is able to conjugate bile acids it allows leakage into the blood stream. In contrast, the results for rats subjected to PH indicated that liver cells during DNA synthesis are not capable of conjugating all free bile acids with taurine although a similar leakage occurs. It is concluded that obvious elevation of serum TCA or CA and biliary T beta MCA could be a useful indicator of hepatocellular proliferation.

Animals↗
PubMed1990

A case of congenital factor V deficiency combined with multiple congenital anomalies: successful management of palatoplasty.

A patient with congenital factor V deficiency combined with mental retardation and several congenital anomalies including cleft palate, dwarfism, microcephaly and right hydrocele testis is described. The levels of factor V activity and factor V antigen of plasma were significantly decreased. The platelet lysate obtained from him also showed a significantly low level of factor V activity. Palatoplasty and tooth extraction were successfully performed under transfusion therapy with fresh-frozen plasma.

Abnormalities, Multiple↗
PubMed1990

Inhibitory effect of antineoplaston A-10 on breast cancer transplanted to athymic mice and human hepatocellular carcinoma cell lines. The members of Antineoplaston Study Group.

The inhibitory effect of Antineoplaston A-10 was tested on the growth curve of human breast cancer (R-27) serially transplanted to athymic mice and on the cell growth of human hepatocellular carcinomas (KMCH-1, KYN-1, KIM-1). Approximately 1.25% of Antineoplaston A-10 in the regular mouse diet (CE2) inhibited the growth curve significantly after 35 days treatment (p less than 0.05). Seventy milligrams of daily intraperitoneal administration of Antineoplaston A-10 Injection also inhibited the growth curve of R-27 after 52 days treatment (p less than 0.01). Histological study of tumor showed no essential difference in structure but significant decrease in number of mitoses in the Antineoplaston A-10 treated groups. The cell growth of human hepatocellular carcinoma cell lines KMCH-1, KYN-1 and KIM-1 was inhibited by Antineoplaston A-10 Injection dose dependently.

Administration, Oral↗
PubMed1990

[Intraoperative ischemic change demonstrated on lead V5 related to hemodynamic episodes as well as sites and degree of coronary vascular lesion].

Electrocardiographic (ECG) changes demonstrated on lead V5 were investigated regarding the effect of hemodynamic change as well as site and degree of the LAD stenosis. Results were summarized as follows. 1. Myocardial ischemic changes on lead V5 occurred in the patients with two or more stenosis on LAD when heart rate increased. 2. Total occlusion of LAD with collaterals from stenosed RCA showed ischemic change on hypotension due to partial perfusion of cardiopulmonary bypass. 3. Ischemic changes occurred in patients with spontaneous angina and non-transmural myocardial infarction when the pericardium was opened. 4. Induction of anesthesia with fentanyl and droperidol kept blood pressure lower, but with this method no ischemic change on lead V5 occurred before CPB.

Aged↗
PubMed1989

Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1.

The incidence and association with 10-year survival of amplification in five protooncogenes or transforming genes were retrospectively examined using DNAs extracted from formalin-fixed, paraffin-embedded blocks of tissues obtained from 176 consecutive patients surgically treated for primary breast carcinoma. The incidences of greater than threefold amplification of hst-1, int-2, c-erbB-2, ear-1 (one of c-erbA), and c-myc were 12, 13, 16, 10, and 4.0%, respectively. hst-1 and int-2 were almost always coamplified (21/22), while c-erbB-2 and ear-1 were frequently coamplified (18/28) with almost the same copy number. The hst-1 and int-2 pair and the c-erbB-2 and ear-1 pair, localized on chromosomes 11q13 and 17q21-22, respectively, in normal cells, were inferred to be constituents of different amplification units. Amplification of hst-1 and/or int-2 was detected preferentially in the younger age group, and was correlated with poorer prognosis in cases carrying four or more copies of the genes. Amplification of c-erbB-2 and/or ear-1 was strongly correlated with poor prognosis in all 176 patients, especially those with lymph node metastasis. Amplification of c-myc was also correlated with poor prognosis. Cox's life-table regression analysis showed that amplification of c-erbB-2 had a prognostic value, which was independent of other known prognostic factors such as lymph node status and tumor size.

Breast Neoplasms↗